MECHANISM OF INDUCTION OF IMMUNOLOGICAL TOLERANCE

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Abstract
Summary: The purpose of the experiments was to study the distribution and fate of a population of antigen molecules responsible for the induction of a state of immunological tolerance in the newborn rat. Salmonella flagellin and other antigens were labelled with carrier‐free I125 to give substitution rate approaching or exceeding 1 radioactive atom per molecule. Tolerance was induced in 2 ways: either by a single injection of a dose of about 100 μg or by a course of injections of 1 μg given twice per week for 8 weeks. Rats were killed at intervals and the antigen distribution pattern was studied by scintillation counting and autoradiography.The results showed that antigen handling in the newborn rat was substantially different from that previously reported in adult rats. Phagocytosis of antigen was never a prominent feature in newborn rats, even when opsonins in the form of immune serum had been passively injected. The outstanding feature was an extremely diffuse distribution of antigen throughout all lymphoid tissues, including the thymus.In rats receiving a single, large dose of antigen at birth, the initial concen tration of antigen scattered diffusely throughout the lymphoid, system was high. Autoradiographs suggested the presence of thousands of molecules per cell. This level fell progressively over the next few weeks, reaching a concentration of around 1 molecule per cell by 3 to 4 weeks. Scattered antigen was also seen in the tissues of rats receiving the twice weekly injections, but these tended to develop the adult pattern of antigen localization as they matured.In both types of experiment, detectable labelled antigen disappeared from the lymphoid system before tolerance was totally lost.
Funding Information
  • U.S. Public Health Service